Elevated CD14 ++ CD16 + Monocytes in Hyperhomocysteinemia-Associated Insulin Resistance in Polycystic Ovary Syndrome

摘要

Background: Hyperhomocysteinemia, chronic low-grade inflammation, and insulin resistance are predominant features in women with polycystic ovary syndrome (PCOS). CD14~(++)CD16~(+)inflammatory monocytes are elevated in cardiovascular diseases and diabetes, in which inflammation is one of the pathogenesis. We aimed to determine whether homocysteine levels are associated with monocyte subtypes or insulin resistance in women with PCOS. Methods: A cross-sectional study was conducted between December 2014 and June 2015 at Peking University Third Hospital. Among 196 Chinese patients with PCOS enrolled, 102 had homocysteine levels ≥10 μmol/L and 94 exhibited normal homocysteine levels. Monocyte surface markers and related cytokines were detected in peripheral blood samples using a flow cytometry, and data on insulin resistance and homocysteine levels were collected. Results: Our results showed that fasting insulin and homeostasis model assessment indices that reflect the severity of insulin resistance were increased in the hyperhomocysteinemia PCOS group. Simple linear regression analysis revealed that homocysteine level is one of the influence factors of insulin resistance in PCOS. Compared with the normal homocysteine group, patients with hyperhomocysteinemia had increased numbers of CD14~(++)CD16~(+)inflammatory monocyte in their peripheral blood and elevated plasma levels of interleukin-1β and interleukin-6, 2 typical cytokines secreted by the inflammatory monocytes. Unlike CD14~(+)CD16~(++)nonclassical monocytes, CD14~(++)CD16~(+)inflammatory monocytes are characterized by high expression of Human leukocyte antigen-antigen D related (HLA-DR). Conclusions: Our findings indicate that CD14~(++)CD16~(+)inflammatory monocytes are associated with hyperhomocysteinemia and insulin resistance in patients with PCOS. Notably, CD14~(++)CD16~(+)monocytes may contribute to the pathogenesis of insulin resistance in women with PCOS.